The following discussion of the background of the invention is merely provided to aid the reader in understanding the invention and is not admitted to describe or constitute prior art to the present invention.
Stroke is a manifestation of vascular injury to the brain which is commonly secondary to atherosclerosis or hypertension, and is the third leading cause of death (and the second most common cause of neurologic disability) in the United States. Stroke can be categorized into two broad types, “ischemic stroke” and “hemorrhagic stroke.” Additionally, a patient may experience transient ischemic attacks, which share the same underlying cause as strokes and which cause the same symptoms. The similarity of these acute clinical syndromes made it difficult to differentiate them; they were distinguished on the basis of an arbitrary criterion for the duration of symptoms. While the damage from a TIA may be just as severe as a stroke, the symptoms of a TIA can resolve within a few minutes or 24 hours. For purposes of the present invention, ischemic stroke and hemorrhagic stroke and TIA will all be referred to as “strokes.”
Ischemic brain injury encompasses thrombotic, embolic, lacunar and hypoperfusion types of strokes. Thrombi are occlusions of arteries created in situ within the brain, while emboli are occlusions caused by material from a distant source, such as the heart and major vessels, often dislodged due to myocardial infarct or atrial fibrillation. Less frequently, thrombi may also result from vascular inflammation due to disorders such as meningitis. Thrombi or emboli can result from atherosclerosis or other disorders, for example, arteritis, and lead to physical obstruction of arterial blood supply to the brain. Lacunar stroke refers to an infarct within non-cortical regions of the brain. Hypoperfusion embodies diffuse injury caused by non-localized cerebral ischemia, typically caused by myocardial infarction and arrhythmia.
The onset of ischemic brain injury is often abrupt, and can become an “evolving stroke” manifested by neurologic deficits that worsen over a 24-48 hour period. In evolving stroke, “stroke-associated symptom(s)” commonly include unilateral neurologic dysfunction that extends progressively, without producing headache or fever. Evolving stroke may also become a “completed stroke,” in which symptoms develop rapidly and are maximal within a few minutes.
Hemorrhagic stroke is caused by intracerebral or subarachnoid hemorrhage, i.e., bleeding into brain tissue, following blood vessel rupture within the brain. Intracerebral and subarachnoid hemorrhages are subsets of a broader category of hemorrhage referred to as intracranial hemorrhage. Intracerebral hemorrhage is typically due to chronic hypertension, and a resulting rupture of an arteriosclerotic vessel. Stroke-associated symptom(s) of intracerebral hemorrhage are abrupt, with the onset of headache and steadily increasing neurological deficits. Nausea, vomiting, delirium, seizures and loss of consciousness are additional common stroke-associated symptoms.
In contrast, most subarachnoid hemorrhage is caused by head trauma or aneurysm rupture which is accompanied by high pressure blood release which also causes direct cellular trauma. Prior to rupture, aneurysms may be asymptomatic, or occasionally associated with tension or migraine headaches. However, headache typically becomes acute and severe upon rupture, and may be accompanied by varying degrees of neurological deficit, vomiting, dizziness, and altered pulse and respiratory rates.
Concepts of brain ischemia and the temporal correlation with clinical events have changed considerably on the basis of studies using computed tomography (CT), magnetic resonance imaging (MRI), positron-emission tomography, and other imaging techniques. At most institutions, CT of the brain is performed as part of the initial evaluation of a patient with suspected stroke. The main advantage of this imaging modality is its widespread availability and sensitivity for hemorrhage. However, it is insensitive to early ischemic changes during acute cerebral ischemia. Several technologies based on MRI have shown promise for the early diagnosis of stroke. However, as a practical issue, most hospitals lack the necessary specialized MRI services in the acute setting.
Another approach to the diagnosis of acute stroke has been the evaluation of biomarkers in body fluid samples such as blood. By way of example, acute stroke has been associated with serum elevations of numerous biomarkers related to inflammation, coagulation, and glial cell damage in a variety of research studies. To date, however, no biomarker test has been demonstrated to possess the requisite sensitivity and specificity to allow it to function as a useful clinical diagnostic.
There remains a need in the art for a rapid, objective, clinically accurate, available diagnostic tool for aiding in the diagnosis and care of stroke patients.